tbuckley/cabot-search huggingface dataset:
Burden of Cardiovascular Disease in Immune Checkpoint Inhibitor–Treated Patients
Authors: Lavanya Kondapalli, Judith Hsia, Ronni Miller, Thomas W. Flaig, Marc P. Bonaca
Journal: JACC CardioOncology (2022)

There is growing recognition of the risk of cardiovascular (CV) events, particularly myocarditis, in the context of immune checkpoint inhibitor (ICI) therapy; however, true event rates in real-world populations and in the background of CV disease remain uncertain.The authors sought to determine CV event occurrence in ICI-treated patients and assess the accuracy of diagnosis by International Classification of Diseases (ICD) code compared with adjudication using established definitions and full-source documentation review.Electronic medical record extraction identified potential CV events in ICI-treated patients in the University of Colorado Health system. Two cardiologists independently adjudicated events using standardized definitions. Agreement between ICD codes and adjudicated diagnoses was assessed using the kappa statistic.The cohort comprised 1,813 ICI-treated patients with a mean follow-up of 4.6 ± 3.4 years (3.2 ± 3.2 years pre-ICI and 1.4 ± 1.4 years post-ICI). Venous thromboembolic events (VTEs) were the most common event, occurring in 11.4% of patients pre-ICI and 11.3% post-ICI therapy. Post-ICI therapy, the crude rates of myocardial infarction (MI), heart failure, and stroke were 3.0%, 2.8%, and 1.6%, respectively. Six patients (0.3%) developed myocarditis post-ICI. Agreement between the ICD code and adjudication was greater for VTE (κ = 0.82; 95% CI: 0.79-0.85) and MI (κ = 0.74; 95% CI: 0.66-0.82) and worse for myocarditis (κ = 0.50; 95% CI: 0.20-0.80) and heart failure (κ = 0.47; 95% CI: 0.40-0.54).ICD codes correlated well with adjudicated events for VTE and MI, but correlation was worse for heart failure and myocarditis. Adjudication with standardized definitions can enhance the understanding of the incidence of CV events related to ICI therapy.
What Is the Evidence of the Diagnostic Criteria and Screening of Immune Checkpoint Inhibitor–Induced Myocarditis?
Authors: Franck Thuny, Marc P. Bonaca, Jennifer Cautela
Journal: JACC CardioOncology (2022)

• Myocarditis is a rare, but serious, complication of immune checkpoint inhibitor therapy. • The diagnosis of immune checkpoint inhibitor–induced myocarditis is sometimes challenging because of clinical, biological, and imaging features. • Diagnostic criteria have been proposed to help clinicians, but have never been validated to date. • Some guidelines now recommend early detection by repeated troponin and ECG testing, but its role has not yet been clearly demonstrated.
Fulminant Cardiotoxicity in a Patient With Cardiac Lymphoma Treated With CAR-T Cells
Authors: Christian Koch, Giulia Montrasio, Benedikt Florian Scherr, Roman Schimmer, Christian M. Matter, Karl Philipp Bühler, Markus G. Manz, Antonia M.S. Müller
Journal: JACC CardioOncology (2022)
Immune Checkpoint Inhibitor Myocarditis and Cellular Rejection in Orthotopic Heart Transplant Recipients
Authors: Timothy Yeung, Catriona McLean, David M. Kaye, Angeline Leet, Hitesh C. Patel, Peter Bergin, Caitlin Cheshire, James L. Hare, Andrew J. Taylor, Sarah Gutman
Journal: JACC CardioOncology (2022)
Successful CAR T Cell Therapy in a Heart and Kidney Transplant Recipient With Refractory PTLD
Authors: Daniel Oren, Ersilia M. DeFilippis, Dor Lotan, Kevin J. Clerkin, Justin Fried, Ran Reshef, Hilda Fernandez, Edward Lin, Jennifer Amengual, Gabriel Sayer, Nir Uriel, Jayant K. Raikhelkar
Journal: JACC CardioOncology (2022)
Monkeypox outbreak, vaccination, and treatment implications for the dermatologic patient: Review and interim guidance from the Medical Dermatology Society
Authors: Anusha M. Kumar, Steven T. Chen, Joseph F. Merola, Arash Mostaghimi, Xiaolong A. Zhou, Nicole Fett, Gideon P. Smith, Arturo P. Saavedra, Megan H. Noe, Misha Rosenbach
Journal: Journal of the American Academy of Dermatology (2022)
Whole-Exome Sequencing Among Chinese Patients With Hereditary Diffuse Gastric Cancer
Authors: Ze-Xian Liu, Xiao-Long Zhang, Qi Zhao, Yungchang Chen, Hui Sheng, Cai-Yun He, Yu-Ting Sun, Ming-Yu Lai, Min-Qing Wu, Zhi-Xiang Zuo, Wei Wang, Zhi-Wei Zhou, Feng-Hua Wang, Yu-Hong Li, Rui-Hua Xu, Miao-Zhen Qiu
Journal: JAMA Network Open (2022)

Importance The E-cadherin gene, CDH1 , and the α-E-catenin gene, CTNNA1 , were previously identified as hereditary diffuse gastric cancer (HDGC) susceptibility genes, explaining 25% to 50% of HDGC cases. The genetic basis underlying disease susceptibility in the remaining 50% to 75% of patients with HDGC is still unknown. Objective To assess the incidence rate of CDH1 germline alterations in HDGC, identify new susceptibility genes that can be used for screening of HDGC, and provide a genetic landscape for HDGC. Design, Setting, and Participants This cohort study conducted retrospective whole-exome and targeted sequencing of 284 leukocyte samples and 186 paired tumor samples from Chinese patients with HDGC over a long follow-up period (median, 21.7 [range, 0.6-185.9] months). Among 10 431 patients diagnosed with gastric cancer between January 1, 2002, and August 31, 2018, 284 patients who met the criteria for HDGC were included. Data were analyzed from August 1 to 30, 2020. Main Outcomes and Measures Incidence rate of CDH1 germline alterations, identification of new HDGC susceptibility genes, and genetic landscape of HDGC. Results Among 284 Chinese patients, 161 (56.7%) were female, and the median age was 35 (range, 20-75) years. The frequency of CDH1 germline alterations was 2.8%, whereas the frequency of CDH1 somatic alterations was 25.3%. The genes with the highest incidence (&amp;amp;gt;10%) of private germline alterations (including insertions and deletions) in the HDGC cohort were MUC4 , ABCA13 , ZNF469 , FCGBP , IGFN1 , RNF213 , and SSPO , whereas previously reported germline alterations of CTNNA1 , BRCA2 , STK11 , PRSS1 , ATM , MSR1 , PALB2 , BRCA1 , and RAD51C were observed at low frequencies (median, 4 [range, 1-12] cases). Furthermore, enrichment of the somatic variant signature of exposure to aflatoxin suggested potential interaction between genetics and environment in HDGC. Double-hit events in genes such as CACNA1D were observed, which suggested that these events might serve as important mechanisms for HDGC tumorigenesis. In addition, germline variants of FSIP2 , HSPG2 , and NCKAP5 and somatic alterations of FGFR3 , ASPSCR1 , CIC , DGCR8 , and LZTR1 were associated with poor overall survival among patients with HDGC. Conclusions and Relevance This study provided a genetic landscape for HDGC. The study’s findings challenged the previously reported high germline alteration rate of CDH1 in HDGC and identified new potential susceptibility genes. Analyses of variant signatures and double-hit events revealed potentially important mechanisms for HDGC tumorigenesis. Findings from the present study may provide helpful information for further investigations of HDGC.
Characterization of Problematic Alcohol Use Among Physicians: A Systematic Review
Authors: Janet Wilson, Peter Tanuseputro, Daniel T. Myran, Shan Dhaliwal, Junayd Hussain, Patrick Tang, Salmi Noor, Rhiannon L. Roberts, Marco Solmi, Manish M. Sood
Journal: JAMA Network Open (2022)

Importance Problematic alcohol use in physicians poses a serious concern to physicians' health and their ability to provide care. Understanding the extent and characteristics of physicians with problematic alcohol use will help inform interventions. Objective To estimate the extent of problematic alcohol use in physicians and how it differs by physician sex, age, medical specialty, and career stage (eg, residency vs practicing physician). Evidence Review Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA ) 2020-compliant systematic review, searching Medline, Embase, and PsychInfo from January 2006 to March 2020. Search terms included Medical Subject Headings terms and keywords related to physicians as the population and problematic alcohol use as the primary outcome. The quality of studies was assessed using the Newcastle-Ottawa Scale. We included articles where problematic alcohol use was measured by a validated tool (ie, Alcohol Use Disorders Identification Test [AUDIT], AUDIT Version C [AUDIT-C], or CAGE [Cut down, Annoyed, Guilty, and Eye-opener] questionnaire) in practicing physicians (ie, residents, fellows, or staff physicians). Findings Thirty-one studies involving 51 680 participants in 17 countries published between January 2006 and March 2020 were included. All study designs were cross-sectional, self-reported surveys. Problematic alcohol use varied widely regardless of measurement method (0 to 34% with AUDIT; 9% to 35% with AUDIT-C; 4% to 22% with CAGE). Reported problematic alcohol use increased over time from 16.3% in 2006 to 2010 to 26.8% in 2017 to 2020. The extent of problematic use by sex was examined in 19 studies, by age in 12 studies, by specialty in 7 studies, and by career stage in 5 studies. Seven of 19 studies (37%) identified that problematic alcohol use was more common in males than females. Based on the wide heterogeneity of methods for included studies, limited conclusions can be made on how problematic alcohol use varies based on physician age, sex, specialty, and career stage. Conclusions and Relevance Studies about problematic alcohol use in physicians demonstrate a high degree of heterogeneity in terms of methods of measurement, definitions for problematic alcohol use, and cohorts assessed. Most studies are primarily self-reported, precluding the ability to determine the true prevalence among the profession. Few studies provide relevant comparisons to aid in identifying key risk groups for targeted interventions.
Comparison of Mitochondrial Adenosine Triphosphate–Sensitive Potassium Channel High- vs Low-Affinity Sulfonylureas and Cardiovascular Outcomes in Patients With Type 2 Diabetes Treated With Metformin
Authors: Meng-Ting Wang, Hsueh-Yi Pan, Ya-Ling Huang, Li-Wei Wu, Pin-Chun Wang, Yu-Juei Hsu, Tzu-Chieh Lin, ChenWei Lin, Jyun-Heng Lai, Chien-Hsing Lee
Journal: JAMA Network Open (2022)

Importance Sulfonylureas are frequently used as add-on to metformin in type 2 diabetes (T2D), and individual sulfonylurea agents carry different risks of cardiovascular disease. Sulfonylureas’ different affinities to cardiac mitochondrial adenosine triphosphate–sensitive potassium (mitoK ATP ) channels have been speculated to account for the intraclass difference in cardiovascular risk from in vitro and ex vivo studies; however, this hypothesis has not been assessed in a general population with diabetes receiving sulfonylureas added to metformin. Objective To compare the risk of myocardial infarction (MI), ischemic stroke, or cardiovascular death in patients with T2D treated with mitoK ATP channel high-affinity sulfonylureas and low-affinity sulfonylureas as add-on to metformin. Design, Setting, and Participants This is a new-user, active-comparator, and propensity score–matched cohort study with analysis of the Taiwanese Diabetes Mellitus Health Database from 2006, to 2017. Data analysis was performed from August 2020 to July 2021. Exposures Cardiac mitoK ATP channel high-affinity (glyburide and glipizide) and low-affinity (gliclazide and glimepiride) sulfonylureas combined with metformin. Main Outcomes and Measures Primary outcome was major adverse cardiovascular events (MACEs), a composite of cardiovascular death or hospitalization for either MI or ischemic stroke. Secondary outcomes included individual MACE components, heart failure, arrhythmia, all-cause mortality, and severe hypoglycemia. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs). Results Each sulfonylurea group comprised 53 714 patients (mean [SD] age, 54.7 [12.1] years; 31 962 men [59.5%]). MitoK ATP channel high-affinity sulfonylureas vs low-affinity sulfonylureas when combined with metformin were associated with an increased risk of MACE (aHR, 1.18; 95% CI, 1.03-1.34), MI (aHR, 1.34; 95% CI, 1.04-1.73), all-cause mortality (aHR, 1.27; 95% CI, 1.03-1.57), and severe hypoglycemia (aHR, 1.82; 95% CI, 1.58-2.10), but not with increased risks of ischemic stroke, cardiovascular death, arrhythmia, and heart failure. The duration analyses revealed the highest MACE risk during 1 to 90 days after initiation of mitoK ATP channel high-affinity sulfonylureas (aHR, 6.06; 95% CI, 4.86-7.55). Conclusions and Relevance Use of mitoK ATP channel high-affinity sulfonylureas vs low-affinity sulfonylureas was associated with an increased MACE risk in patients with T2D concomitantly receiving metformin, suggesting that high-affinity blockage of the mitoK ATP channels could account for sulfonylurea-associated MACEs.
Comparison of Clinical Study Results Reported in medRxiv Preprints vs Peer-reviewed Journal Articles
Authors: Guneet Janda, Vishal Khetpal, Xiaoting Shi, Joseph S. Ross, Joshua D. Wallach
Journal: JAMA Network Open (2022)

Preprints have been widely adopted to enhance the timely dissemination of research across many scientific fields. Concerns remain that early, public access to preliminary medical research has the potential to propagate misleading or faulty research that has been conducted or interpreted in error. To evaluate the concordance among study characteristics, results, and interpretations described in preprints of clinical studies posted to medRxiv that are subsequently published in peer-reviewed journals (preprint-journal article pairs). This cross-sectional study assessed all preprints describing clinical studies that were initially posted to medRxiv in September 2020 and subsequently published in a peer-reviewed journal as of September 15, 2022. For preprint-journal article pairs describing clinical trials, observational studies, and meta-analyses that measured health-related outcomes, the sample size, primary end points, corresponding results, and overarching conclusions were abstracted and compared. Sample size and results from primary end points were considered concordant if they had exact numerical equivalence. Among 1399 preprints first posted on medRxiv in September 2020, a total of 1077 (77.0%) had been published as of September 15, 2022, a median of 6 months (IQR, 3-8 months) after preprint posting. Of the 547 preprint-journal article pairs describing clinical trials, observational studies, or meta-analyses, 293 (53.6%) were related to COVID-19. Of the 535 pairs reporting sample sizes in both sources, 462 (86.4%) were concordant; 43 (58.9%) of the 73 pairs with discordant sample sizes had larger samples in the journal publication. There were 534 pairs (97.6%) with concordant and 13 pairs (2.4%) with discordant primary end points. Of the 535 pairs with numerical results for the primary end points, 434 (81.1%) had concordant primary end point results; 66 of the 101 discordant pairs (65.3%) had effect estimates that were in the same direction and were statistically consistent. Overall, 526 pairs (96.2%) had concordant study interpretations, including 82 of the 101 pairs (81.2%) with discordant primary end point results. Most clinical studies posted as preprints on medRxiv and subsequently published in peer-reviewed journals had concordant study characteristics, results, and final interpretations. With more than three-fourths of preprints published in journals within 24 months, these results may suggest that many preprints report findings that are consistent with the final peer-reviewed publications.
Seven-Year Durability of Improvements in Urinary Incontinence After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy
Authors: Wendy C. King, Amanda S. Hinerman, Leslee L. Subak
Journal: JAMA Network Open (2022)

This cohort study evaluates the durability of improvements in urinary incontinence among women and men who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy.
ESGE news and upcoming events January 2023
Journal: Endoscopy (2022)

After more than two years of pandemic and a virtual congress in 2021 we were thrilled to be able to hold ESGE Days 2022 as a hybrid meeting in Prague. What a success! More than 3000 participants enjoyed the event. Covid-19 was still present and challenged our organisation, however, this was not the biggest hurdle. In February we were faced with a war in the middle of Europe. ESGE was one of the first societies to show solidarity with our Ukrainian colleagues by suspending the Russian Society of Endoscopy’s ESGE membership. ESGE stands for diversity, peace and democracy and all endoscopists who support this are welcome in our society.
Is post-endoscopic ultrasound pancreatic cancer analogous to post-colonoscopy colorectal cancer?
Authors: Deepak Madhu, Syed Anjum Gardezi, Nadeem Tehami
Journal: Endoscopy (2022)

See also: Rate of pancreatic cancer following a negative endoscopic ultrasound and associated factorsEndoscopy 2022; 54(11): 1053-1061DOI: 10.1055/a-1784-1661
Reply to Madhu et al.
Authors: Dominic King, Kofi W. Oppong, Nigel Trudgill
Journal: Endoscopy (2022)

See also: Rate of pancreatic cancer following a negative endoscopic ultrasound and associated factorsEndoscopy 2022; 54(11): 1053-1061DOI: 10.1055/a-1784-1661 Letter to: Is post-endoscopic ultrasound pancreatic cancer analogous to post-colonoscopy colorectal cancer?Endoscopy 2023; 55(01): 102-102DOI: 10.1055/a-1881-4533
Endoscopy International Open – recently published
Journal: Endoscopy (2022)

Comment on: Endoscopic treatment of intussusception due to small intestine polyps in patients with Peutz-Jeghers SyndromeEndosc Int Open 2022; 10(12): E1583-E1588DOI: 10.1055/a-1954-0110 Comment on: Feasibility of progressive polyp contraction with underwater endoscopic mucosal resection in ≥ 20 mm superficial colorectal lesionsEndosc Int Open 2022; 10(12): E1577-E1582DOI: 10.1055/a-1955-3379 Comment on: A new system to prevent SARS-CoV-2 and microorganism air transmission through the air circulation system of endoscopesEndosc Int Open 2022; 10(12): E1589-E1594DOI: 10.1055/a-1907-3939
A case for investment in clinical metagenomics in low-income and middle-income countries
Authors: Gert Marais, Diana Hardie, Adrian Brink
Journal: The Lancet Microbe (2022)

Clinical metagenomics is the diagnostic approach with the broadest capacity to detect both known and novel pathogens. Clinical metagenomics is costly to run and requires infrastructure, but the use of next-generation sequencing for SARS-CoV-2 molecular epidemiology in low-income and middle-income countries (LMICs) offers an opportunity to direct this infrastructure to the establishment of clinical metagenomics programmes. Local implementation of clinical metagenomics is important to create relevant systems and evaluate cost-effective methodologies for its use, as well as to ensure that reference databases and result interpretation tools are appropriate to local epidemiology. Rational implementation, based on the needs of LMICs and the available resources, could ultimately improve individual patient care in instances in which available diagnostics are inadequate and supplement emerging infectious disease surveillance systems to ensure the next pandemic pathogen is quickly identified.
Cost-effectiveness of voluntary medical male circumcision for HIV prevention across sub-Saharan Africa: results from five independent models
Authors: Loveleen Bansi-Matharu, Edinah Mudimu, Rowan Martin-Hughes, Matt Hamilton, Leigh Johnson, Debra ten Brink, John Stover, Gesine Meyer-Rath, Sherrie L Kelly, Lise Jamieson, Valentina Cambiano, Andreas Jahn, Frances M Cowan, Collin Mangenah, Webster Mavhu, Thato Chidarikire, Carlos Toledo, Paul Revill, Maaya Sundaram, Karin Hatzold, Aisha Yansaneh, Tsitsi Apollo, Thoko Kalua, Owen Mugurungi, Valerian Kiggundu, Shufang Zhang, Rose Nyirenda, Andrew Phillips, Katharine Kripke, Anna Bershteyn
Journal: The Lancet Global Health (2022)

Voluntary medical male circumcision (VMMC) has been a recommended HIV prevention strategy in sub-Saharan Africa since 2007, particularly in countries with high HIV prevalence. However, given the scale-up of antiretroviral therapy programmes, it is not clear whether VMMC still represents a cost-effective use of scarce HIV programme resources.
Recruiting T cells and sensitizing tumors to NKG2D immune surveillance for robust antitumor immune response
Authors: Xiang Li, Xuemeng Guo, Jiaxin Huang, Qing Lin, Bing Qin, Mengshi Jiang, Xinyu Shan, Zhenyu Luo, Junlei Zhang, Yingying Shi, Yichao Lu, Xu Liu, Yongzhong Du, Fuchun Yang, Lihua Luo, Jian You
Journal: Journal of Controlled Release (2022)
Peripheral Microneedle Patch for First‐Aid Hemostasis
Authors: Jungho Lee, Sebin Park, Phuong Thao Le, Geunho Lee, Hyoun Wook Lee, Gaeun Yun, Juhyeong Jeon, Jeongwoo Park, Duy Tho Pham, Young Sook Park, Hoon Lim, Chulhong Kim, Tae Sik Hwang, Seung Whan Kim, Geunbae Lim
Journal: Advanced Healthcare Materials (2022)

Despite the minimized puncture sizes and high efficiency, microneedle (MN) patches have not been used to inject hemostatic drugs into bleeding wounds because they easily destroy capillaries when a tissue is pierced. In this study, a shelf-stable dissolving MN patch is developed to prevent rebleeding during an emergency treatment. A minimally and site-selectively invasive hemostatic drug delivery system is established by using a peripheral MN (p-MN) patch that does not directly intrude the wound site but enables topical drug absorption in the damaged capillaries. The invasiveness of MNs is histologically examined by using a bleeding liver of a Sprague-Dawley (SD) rat as an extreme wound model in vivo. The skin penetration force is quantified to demonstrate that the administration of the p-MN patch is milder than that of the conventional MN patch. Hemostatic performance is systematically studied by analyzing bleeding weight and time and comparing them with that of conventional hemostasis methods. The superior performance of a p-MN for the heparin-pretreated SD rat model is demonstrated by intravenous injection in vivo.
Mediation of the Same Epigenetic and Transcriptional Effect by Independent Osteoarthritis Risk–Conferring Alleles on a Shared Target Gene, <scp><i>COLGALT2</i></scp>
Authors: Yulia S. Kehayova, J. Mark Wilkinson, Sarah J. Rice, John Loughlin
Journal: Arthritis & Rheumatology (2022)

Over 100 DNA variants have been associated with osteoarthritis (OA), including rs1046934, located within a linkage disequilibrium block encompassing part of COLGALT2 and TSEN15. The present study was undertaken to determine the target gene(s) and the mechanism of action of the OA locus using human fetal cartilage, cartilage from OA and femoral neck fracture arthroplasty patients, and a chondrocyte cell model.